The present invention relates to a method of manufacturing calcium phosphate powders such as xcex2-tricalcium phosphate and hydroxy calcium phosphate or the like that are suitable for biomaterials, and more particularly relates to a method of manufacturing the calcium phosphate powders that are capable of easily manufacturing the calcium phosphate powders having an excellent characteristics through a simple manufacturing process, and capable of greatly reducing a manufacturing cost of the calcium phosphates.
Calcium phosphates typically represented by xcex2-tricalcium phosphate [Ca3(PO4)2] and hydroxy calcium phosphate (hydroxy apatite) [Ca10(PO4)6(OH)2] are excellent in suitability to organism structure and have an affinity to organism body, so that calcium phosphates are valuable as bio-ceramic raw materials for constituting artificial bone, artificial tooth, artificial articulate or the like. In addition, calcium phosphates have been widely utilized as materials such as base material for tooth paste, additive for medical product, food additives, material for cosmetic chemist, separating/absorbing material for biopolymer and material for constituting humidity sensor or the like.
Conventionally, these calcium phosphate powders have been manufactured in accordance with the following methods such as wet-way (liquid phase) synthesizing method, dry-way (solid phase) synthesizing method, mechanochemical-reaction synthesizing method or the like. The wet-type synthesizing method is a synthesizing methodin which a calcium solution of calcium nitrate or the like is reacted with a phosphoric acid solution of ammonium hydrogen phosphate, or an amorphous calcium phosphate is produced from a reaction being taken place in heterogeneous system comprising calcium hydroxide and phosphoric acid, then the formed amorphous calcium phosphate is subjected to a calcining treatment thereby to produce xcex2-tricalcium phosphate (xcex2-TCP).
On the other hand, the dry-type synthesizing method is a method in which calcium carbonate is reacted with calcium pyrophosphate in a solid phase at a high temperature thereby to obtain calcium phosphate powder.
On the other hand, in these years, there has been also proposed a manufacturing method comprising simple manufacturing process and utilizing the mechanochemical reaction as a new method of synthesizing the calcium phosphate compound. For example, a publication of examined Japanese Patent Application No. HEI3-69844 and a publication of unexamined Japanese Patent Application No. HEI4-321508 disclose a method in which calcium carbonate powder and calcium hydrogenphosphate powder or dihydrate thereof are mixed to prepare a slurry of which molar ratio (Ca/P) of calcium to phosphor is controlled, then thus obtained slurry is milled by using a ball mill or a vibration mill or the like to cause reaction, thereafter, the reaction product is dried and heat-treated at a high temperature thereby to manufacture crystallized xcex2-tricalcium phosphate (xcex2-TCP).
Further, a publication of unexamined Japanese Patent Application No. HEI4-321508 discloses a method in which xcex2-tricalcium phosphate is heated under a condition of existing water and pressingly treated thereby to manufacture hydroxy calcium phosphate (hydroxy apatite) powder. In this connection, in the conventional process of manufacturing the hydroxy calcium phosphate, a process directly using the mechanochemical reaction has not been adopted.
However, in case of the conventional wet-type synthesizing method, the synthesizing conditions such as the molar ratio of a raw material, treating speed, pH or the like are required to be strictly controlled. On the other hand, there is a difficulty in obtaining a product having a compositional high purity and uniformity. At any rate, for the purpose of obtaining a powder having a compositional high-purity and uniformity, there is posed a problem that the manufacturing cost would be greatly increased.
In contrast, in case of the conventional dry-type synthesizing method, the synthesized calcium phosphate powder has a coarse grain size, so that the powder cannot be directly used as a bio-ceramics raw material and a fine grinding or milling treatment is essentially required whereby there is posed a problem that the manufacturing process becomes complicate and troublesome.
On the other hand, in case of the conventional synthesizing method utilizing the mechanochemical react ion, a long-term grinding process for 1 day to 50 hours is essentially required for advancing the reaction, thereby to cause a problem that the production cost is greatly increased. In addition, in order to smoothly advance the reaction, a solid content of the slurry is required to be set to a lower level. Therefore, there are posed various problems such that an amount of heat energy to be put into the subsequent drying process remarkably increases, a drying operation is required to perform for a long time. In addition, for the purpose of pulverizing or grinding the coarsely aggregated bodies caused by the drying operation, an additional grinding process is essentially required, so that there is posed a fatal problem such that a running cost for the manufacturing facilities and the production cost are greatly increased.
The present invention had been achieved to solve the aforementioned problems and an object of the present invention is to provide a method of manufacturing calcium phosphate powder, the method being capable of easily manufacturing fine calcium phosphate powder having excellent characteristics by a simple manufacturing process and capable of greatly reducing the production cost of the powder.
In order to achieve the aforementioned object, the inventors of the present invention had prepared calcium phosphate powders under various conditions by using various material powders, reacting synthesizing methods and pulverizing devices (grinding machines). Then, through many experiments, the inventors had comparatively reviewed the influences of the differences in the manufacturing conditions onto characteristics and manufacturing cost of calcium phosphate powder as a product.
As a result, the inventors had found and obtained the following knowledge. That is, when calcium hydroxide powder as a raw material is used in place of the conventional calcium carbonate, then the calcium hydroxide powder is mixed to calcium hydrogen phosphate powder thereby to prepare a mixed material, then the mixed material is further mixed and milled to take place a mechanochemical reaction. Thereafter, when the reaction product is heat-treated, there can be obtained knowledge that fine particles of calcium phosphate compound having a high crystallinity and high homogeneity can be effectively manufactured in a short time.
In particular, when a multi-ring media type ultrafine mill comprising a number of ring-shaped milling media is used as a mixing and milling device for advancing a mechanochemical reaction by conducting the mixing and the milling of the mixed material, there could be also obtained the findings such that a reaction activity of the mixed material was increased, and it became possible to rapidly advance the above mechanochemical reaction whereby a production efficiency of the calcium phosphate compound could be remarkably increased.
Furthermore, in the conventional various synthesizing methods conducted in a wet, the solid component content (viscosity) of the mixed material slurry required to be suppressed to a lower level, and the mixed material slurry is required to be mixed and pulverized for a long time. In contrast, when the above ultrafine mill is used, even if the slurry has a high solid content and a high viscosity, there could be also obtained a finding that it becomes possible to mix and pulverize the slurry in a short time whereby the production efficiency of the calcium phosphate compound could be remarkably increased.
The present invention had been achieved on the basis of the above findings. Namely, a method of manufacturing calcium phosphate powder according to the present invention comprises the steps of preparing a mixed material by mixing calcium hydroxide (Ca((OH)2) powder and calcium hydrogenphosphate powder so that a molar ratio (Ca/P) of calcium to phosphor is set to a range of 1.45-1.72; conducting a mixing/milling treatment to the mixed material to cause a soft-mechanochemical compositing reaction thereby to prepare a calcium phosphate precursor; conducting a heat treatment to thus obtained precursor at a temperature of 600xc2x0 C. or more thereby to prepare a calcium phosphate powder.
In the above method, it is preferable that the calcium hydrogenphosphate is at least one compound selected from the group consisting of calcium monohydrogenphosphate (CaHPO4), calcium monohydrogenphosphate dihydrate (CaHPO4.2H2O), calcium dihydrogenphosphate (Ca(H2PO4)2); and calcium dihydrogenphosphate monohydrate (Ca(HPO4)2.H2O).
Further, it is preferable that the calcium phosphate to be prepared after the heat treatment is at least one of xcex2-tricalcium phosphate (TCP) and calcium hydroxyphosphate (hydroxyapatite: HAp). Furthermore, it is also preferable that the molar ratio (Ca/P) of calcium to phosphor contained in the mixed material is set to a range of 1.45-1.55, the calcium phosphate precursor to be formed by the soft-mechanochemical compositing reaction is tricalcium phosphate precursor, and the calcium phosphate to be prepared after the heat treatment is xcex2-tricalcium phosphate.
In addition, it is also preferable that the molar ratio (Ca/P) of calcium to phosphor contained in the mixed material is set to a range of 1.62-1.72, the calcium phosphate precursor to be formed by the soft-mechanochemical compositing reaction is hydroxyapatite (HAp), and the calcium phosphate to be prepared after the heat treatment is calcium hydroxyphosphate.
Further, the mixing/milling treatment for the mixed material may be performed by a dry-process. Furthermore, the mixed material may be prepared in a form of slurry and the mixing/milling treatment for the slurry may be performed by a wet-process. In addition, it is preferable that a content (concentration) of solid component contained in the slurry is set to 15-50 wt %. In particular, it is preferable that the mixing/milling treatment for the mixed material is performed by means of a multi-ring type ultrafine mill comprising a number of ring-shaped pulverizing media.
The present invention adopts a countermeasure in which calcium hydroxide (Ca(OH)2) powder is used as a material in place of calcium carbonate that has been conventionally used as the material, and calcium hydroxide and calcium hydrogenphosphate are mixed and milled so that an inter reaction i.e. soft-mechanochemical reaction between acid-base points at surface of material particles is taken place whereby the calcium phosphate powders such as xcex2-tricalcium phosphate or the like is synthesized in a short time.
More concretely to say, the manufacturing method comprises the steps of preparing a mixed material by weighing and mixing calcium hydroxide (Ca(OH)2) powder and calcium dihydrogenphosphate monohydrate powder or the like so that a molar ratio (Ca/P) of calcium to phosphor is set to a range of 1.45-1.72; putting the mixed material into a vessel of a milling device, mixing and milling the mixed material under predetermined milling conditions to form a precursor, and conducting a heat treatment to the obtained precursor at a temperature of 600xc2x0 C. or more thereby to synthesize fine calcium phosphate powders such as xcex2-tricalcium phosphate, calcium hydroxyphosphate or the like.
In the above method, as the material of the calcium hydrogenphosphate, it is preferable to use at least one compound selected from the group consisting of calcium monohydrogenphosphate (CaHPO4), calcium monohydrogenphosphate dihydrate (CaHPO4.2H2O), calcium dihydrogenphosphate (Ca(H2PO4)2) and calcium dihydrogenphosphate monohydrate (Ca(H2PO4)2.H2O).
The above calcium hydroxide (Ca(OH)2) powder and calcium hydrogenphosphate powder are mixed so that a molar ratio (Ca/P) of calcium to phosphor is set to a range of 1.45-1.72 thereby to prepare the mixed material. In particular, when a mixed material controlled to have a molar ratio of 1.45-1.55 is mixed and milled so that the mechanochemical compositing reaction takes place thereby to form a precursor, then the precursor is subjected to a heat treatment at a temperature of 600xc2x0 C. or more, xcex2-tricalcium phosphate (Ca3(PO4)2) (TCP) is efficiently formed in accordance with the following formulae of (1)-(4):
Ca(OH)2+2CaHPO4xe2x86x92Ca3(PO4) 2+2H2Oxe2x80x83xe2x80x83(1)
Ca(OH)2+2CaHPO42.H2Oxe2x86x92Ca3(PO4)2+6H2Oxe2x80x83xe2x80x83(2)
2Ca(OH)2+Ca(H2PO4)2xe2x86x92Ca3(PO4)2+4H2Oxe2x80x83xe2x80x83(3)
2Ca(OH)2+Ca(H2PO4)2.H2Oxe2x86x92Ca3(PO4)2+5H2Oxe2x80x83xe2x80x83(4)
On the other hand, when a mixed material controlled to have a molar ratio of 1.62-1.72 is mixed and milled so that the mechanochemical compositing reaction is take place thereby to form a precursor, then the precursor is subjected to a heat treatment at a temperature of 600xc2x0 C. or more, calcium hydroxyphosphate (Ca10(PO4)6 (OH)2: hydroxyapatite (HAp)) is efficiently formed in accordance with the following formulae (5)-(8):
4Ca(OH)2+6CaHPO4xe2x86x92Ca10(PO4)6(OH)2+4H2O+H2↑xe2x80x83xe2x80x83(5)
4Ca(OH)2+6CaHPO4.2H2Oxe2x86x92Ca10(PO4)6(OH)2+16H2O+H2↑xe2x80x83xe2x80x83(6)
7Ca(OH)2+3Ca(H2PO4)2xe2x86x92Ca10(PO4)6(OH)2+12H2Oxe2x80x83xe2x80x83(7)
7Ca(OH)2+3Ca(H2PO4)2.H2Oxe2x86x92Ca10(PO4)6(OH)2+15H2Oxe2x80x83xe2x80x83(8)
In addition, it is considered that when a predetermined amount of calcium oxide (CaO) is mixed to the above mixed material, it becomes possible to form tetracalcium phosphate (Ca4(PO4)2.O:TTCP) in accordance with the following formulae (9) and (10):
Ca(OH)2+2CaHPO4+CaOxe2x86x92Ca4(PO4)2.O+2H2Oxe2x80x83xe2x80x83(9)
2Ca(OH)2+Ca(H2PO4)2.H2O+CaOxe2x86x92Ca4(PO4)2.O+5H2Oxe2x80x83xe2x80x83(10)
In addition, it is considered that when a predetermined amount of calcium fluoride (CaF2) is mixed to the above mixed material, it becomes possible to form fluorine apatite (Ca10(PO4)6F2) in accordance with the following formulae (11) and (12):
3Ca(OH)2+6CaHPO4+CaF2xe2x86x92Ca10(PO4)6F2+3H2Oxe2x80x83xe2x80x83(11)
xe2x80x836Ca(OH)2+3Ca(H2PO4)2.H2O+CaF2xe2x86x92Ca10(PO4)6F2+12H2Oxe2x80x83xe2x80x83(12)
In the manufacturing method of this invention, when the soft-mechanochemical reaction is advanced in the process of mixing and milling the mixed material, the above various calcium phosphate precursors are formed. The above mechanochemical compositing reaction can be advanced as a solid phase reaction in a dry-process in which a material powder is mixed and milled without adding a dispersing medium to the material powder. On the other hand, the compositing reaction can be also advanced as a liquid phase reaction in a wet-process in which a slurry prepared by dispersing the mixed material powder in a solvent is mixed and milled.
As the milling device for promoting the soft-mechanochemical compositing reaction by mixing and pulverizing the above mixed material, a motor-driven mortar, a vibration mill and a planetary ball mill or the like are considered to be adopted. However, in these milling devices, a centrifugal effect is relatively small, and mechanical stress and impacting forces to be imparted to the material are insufficient. Therefore, even if the milling operation is carried out for about one hour or so, it is very difficult to impart sufficient reaction activity to the mixed material and also difficult to advance the soft-mechanochemical reaction. For this reason, in general, the reaction activity cannot be imparted to the mixed material powder until the material slurry is subjected to the treatment for a long time of about 10-50 hours or more. Accordingly, the above milling devices are not considered to be effective for simplifying the manufacturing processes.
Therefore, in the manufacturing method of the present invention, it is preferable to adopt various impacting-type grinding mills or a powder surface modifying device capable of repeatedly imparting an impacting force to the mixed material in a short time.
In the mixing and milling treatment for advancing the above soft-mechanochemical compositing reaction, the centrifugal effect (Z) to be imparted to the mixed material powder is required to be at least 15. In this connection, the centrifugal effect (Z) is a quantitative index showing a magnitude of pulverizing force, and is a ratio of the centrifugal force (Fc) to a gravitational force (Fg). The centrifugal effect (Z) is expressed by the following formula:
Z=Fc/Fg=rxcfx892/g(xe2x88x92)
wherein r is radius of rotation, xcfx89 is angular speed, and g is gravitational acceleration.
When the centrifugal effect (Z) is less than 15, the impacting force to be imparted to the mixed material is insufficient, and it becomes impossible to increase the reaction activity by forming distortions in crystal structure of the surface portion of the material particles in a short time. Therefore, in order to increase the reaction activity of the mixed material and to prepare the mixed material having a uniformity, it is required to use a milling device capable of imparting impacting force having a centrifugal effect (Z) of 15 or more, preferably 70 or more, and more preferably 150 or more.
In this connection, the method of the present invention therefore uses such an ultrafine mill (multi-ring type pulverizing mill) as shown in FIGS. 1 and 2 as the milling device comprising a number of ring-shaped pulverizing media for rapidly carrying out the soft-mechanochemical compositing treatment. This ultrafine mill is capable of applying impact force and friction to powder particles so as to enhance the reaction activity thereof, and efficiently mixing and milling the powder particles within a short time. The device comprises a cylindrical casing 1, a main shaft 4 which is rotated in the casing 1, and a plurality of sub-shafts 6 which are rotated around the main shaft 4 in linkage with the rotation of the main shaft 4, wherein each of the sub-shafts 6 being provided with many ring members 9 as grinding media. Although the size of each of the ring members 9 as the grinding media depends upon the type and size of the treatment device used, an outer diameter of the member is 25 to 45 mm, and the thickness of the member is several mm. Although the material for constituting the ring members 9 depends upon the physical properties of a material to be processed, the ring members 9 can be composed of stainless steel, ceramic materials such as alumina, zircoma or the like, or a hard carbide material such as WC.
The above casing 1 has an internal peripheral surface 2 having a center axis in a longitudinal direction, and comprises a rotational mechanism 3 provided in the casing 1 serving as a processing chamber. The rotational mechanism 3 comprises the main shaft 4 concentric with the casing 1, a pair of press plates 5 and 5xe2x80x2 which are fixed at a predetermined interval therebetween in the longitudinal direction of the main shaft 4, and the sub-shafts 6 which are fixed by the press plates 5 and 5xe2x80x2 so as to be arranged at the same distance from the main shaft 4 in parallel therewith.
Each of the press plates 5 and 5xe2x80x2 has a form in which the same number of arms as the number of the sub-shafts 6 are radially projected. The form of the press plates 5 and 5xe2x80x2 in which the arms are provided at equal intervals, not a simple disk form, can improve the degree of convection (mixing) of a material to be processed, which is put into the casing 1, and decrease as much as possible the amount of the material to be processed, which is deposited as a dead stock on the upper press plate 5.
Each of the sub-shafts 6 comprises a long bolt-like member having ends that are respectively passed through holes provided at the ends of the arms of both press plates 5 and 5xe2x80x2 and tightened by nuts 7. The upper end of the main shaft 4 is connected directly to a driving Source such as a motor (not shown) or provided with a pulley so that the rotational force of the driving source is transmitted to the main shaft 4 through a V belt.
As shown in FIG. 2, for the purpose of increasing wear resistance, there may be a case where a cylindrical collar 8 is fitted on each of the sub-shafts 6 with a small gap therebetween, and a plurality of ring members 9 are retractably mounted on each of the collar 8. Each of the ring members 9 has an internal diameter sufficiently larger than the outer diameter of the collar 8, and is constructed so as to have a sufficient gap between the internal peripheral surface of the ring member 9 and the external peripheral surface of the collar 8 when the external peripheral surface of the ring member 9 contacts the internal peripheral surface 2 of the casing 1.
The ring members 9 are stacked to form a gap corresponding to the total thickness of 2 to 3 ring members 9 between the upper side of the uppermost ring member 9 and the lower side of the press plate 5, but not closely stacked between both press plates 5 and 5xe2x80x2 without a gap. This stacking structure makes the ring members 9 rotatively around each of the collars 8.
Each of the ring members 9 is formed in a cylindrical form having parallel upper and lower surfaces, which is a so-called washer-like form having smooth upper and lower surfaces, and an outer peripheral surface. If required, the outer peripheral surface may be curved for promoting bite into the powder material.
Agitating blades 10 and 10xe2x80x2 are radially disposed at upper and lower portions of the main shaft 4, which are below the lower press plate 5xe2x80x2 and above the upper press plate 5, respectively, so as to agitate the material to be processed, which is put into the casing 1.
To an upper flange 13 of the casing 1 is fixed an upper cover 11 having a through hole by tightening members such as bolts and nuts, with a packing 12 therebetween. The main shaft 4 is passed through the through hole of the upper cover 11, the through hole being provided with an oil seal 14 for sealing the main shaft 4, and an oil seal holder 15 for holding the oil seal 14. In order to prevent a temperature rise of the material to be processed during grinding, the side of the casing 1 has a jacket structure 16. A refrigerant supply port 17 and discharge port 18 are provided in the jacket 16 so that the material to be processed which is put into the casing 1 can be cooled by continuously supplying any one of various refrigerants into the jacket 16.
In the grinding/milling device (ultrafine mill) constructed as described above, a gap of several millimeters (mm) is formed between the outer periphery of each of the sub-shafts 6 and the inner peripheries of the ring members 9 so that the ring members 9 can be freely independently rotated. The ring members 9 serving as the grinding media are radially moved by an amount corresponding to the gap due to the centrifugal force generated by the rotation of the main shaft 4, and circumferentially rotated in the casing 1 while being pressed on the inner periphery 2 of the casing 1. At the same time, the ring members 9 themselves are rotated around the sub-shafts 6 due to the friction between the inner peripheral surface 2 and the ring members 9. Namely, the ring members 9 are moved in the casing 1 while being repeatedly rotated around the main shaft 4 and each of the sub-shafts 6.
When the raw material mixture powder in an amount corresponding to 10 to 80% of the effective volumes of the grinding portion is put into the casing 1 and then subjected to the soft-mechanochemical treatment by rotating the main shaft 4, the raw material mixture powder is held between the rotating ring members 9 and the internal peripheral surface 2 of the casing 1, and subjected to impact force (compressive force) corresponding to the centrifugal effect caused by the ring members 9 and the grinding/milling function due to the rotation of the ring members 9 themselves. As a result, the raw material mixture powder is ground and dispersed, and, at the same time, strains and distortions are produced in the crystal structure of the particle surfaces of the mixture powder, so that a soft-mechanochemical compositing reaction is rapidly advanced thereby to form a calcium phosphate precursor in which the reactivity of the surfaces of the raw material mixture powder is enhanced. The centrifugal effect Z exerted on the raw material mixture powder is controlled by changing the rotational speed of the main shaft 4.
According to knowledge of the inventors of this invention, it has been confirmed that the soft-mechanochemical compositing reaction to be advanced by mixing and pulverizing the mixed material is greatly influenced by operating conditions such as a kind or magnitude of the mechanical stress, pulverizing mechanism of the milling device, atmosphere for the treatment or the like.
In place of the conventional milling devices such as motor-driven mortar, various ball mills or the like, when there is particularly used a milling device like the above multi-ring media type ultrafine mill having a special pulverizing mechanism provided with a number of ring-shaped pulverizing media, the reactivity of the material mixture can be rapidly increased by the short-time mixing and pulverizing treatment, so that it becomes possible to shorten a required time for the soft-mechanochemical compositing reaction.
In the method of this invention when the mixing/milling operation is performed and acid-base points are formed on surface of the material particles, the soft-mechanochemical reaction is advanced by a reaction mechanism in which new chemical bondings are directly formed by the inter-action between the acid-base points formed on the surfaces of the different material particles, whereby the calcium phosphate precursor is formed. Although this reaction is one kind of a solid-phase reaction, it has a characteristic of exhibiting a high reaction rate, so that a time required for synthesizing calcium phosphate compound can be greatly shortened in comparison with that of the conventional method.
The reaction mechanism of the above soft-mechanochemical reaction mechanism to be used in the method of this invention is quite different from that of the conventional mechanochemical reaction mainly consisting of a liquid-phase reaction disclosed in Japanese Patent Publication No. 3 (1991)-69844 in which a dissolving of solid material is promoted by a wet-type pulverization then a compositing reaction is advanced by a mutual reaction of ions generated in a solution thereby to cause the liquid phase reaction.
That is, the method of this invention is a method wherein acidbase points are generated at the surface of the solid material particles by utilizing the mechanical stress and simultaneously cause the mutual reaction (inter-reaction). In this point, the reaction mechanism used in this invention is also quite different from that of the conventional solid-phase method i.e., a high temperature solid-phase reacting method in which the mutual reaction between the different material particles is advanced by using heat energy thereby to form calcium phosphate compound.
In particular, non-free water such as hydroxyl group and bound water (crystal water) is quite different from free water to be added to the material powder as dispersion medium in the conventional method. The non-free water has a strong function as a catalyser for promoting the mechanochemical compositing reaction to be caused during the mixing and milling the material mixture. Accordingly, when the calcium hydroxide powder having the non-free water i.e., hydroxyl group or calcium hydrogenphosphate having the bound water is used as a starting material like this invention, the mechanochemical reaction can be rapidly advanced in the mixing/milling process thereby to effectively produce calcium phosphate precursor.
The catalytic action by the above non-free waters such as hydroxyl group and the combined water or the like in the soft-mechanochemical reaction is similarly revealed in not only a case where the dry-type mixing/milling operation is performed without adding the non-free water as the dispersing medium but also a case where the wet-type mixing/milling operation is performed to a highly-concentrated material slurry which is prepared by adding the dispersion medium so as to have a solid content of 15-50 wt %, and more preferably to have a solid content of 20-40 wt %.
In particular, when the material mixture to which the dispersion medium such as water is not added is mixed and milled in a dry-process unlike the conventional method, a drying-process is not required to perform to the resulting precursor substance at a stage after the completion of the soft-mechanochemical compositing reaction, so that the precursor substance can be immediately supplied to a heating-treatment process. Therefore, a crystallization of the precursor can be advanced by the heat treatment at a low temperature, so that calcium phosphate compounds such as xcex2-tricalcium phosphate can be manufactured at high efficiency and low cost.
When the precursor substance obtained by the above soft-mechanochemical compositing reaction is subjected to the heat treatment, calcium phosphate compounds such as xcex2-tricalcium phosphate and hydroxy calcium phosphate can be manufactured. The above heat treatment is performed at temperature of 600-800xc2x0 C. for 1-3 hours or at temperature of 900-950xc2x0 C. for 1-10 minutes. Namely, in the heat treatment at 600+ C. or more, when the temperature is set to be low, the time required for the heat treatment is relatively lengthened. On the other hand, when the temperature for the heat treatment is set to be lower than 600xc2x0 C., a part of un-reacted material is left, so that the purity in substantial structure and crystallizing property of the calcium phosphate compound is lowered. When the above temperature and time for the heating treatment are controlled, it becomes possible to adjust and control the purity in substantial structure and crystallinity of xcex2-tricalcium phosphate and hydroxy calcium phosphate.
In the manufacturing method of this invention, for example, calcium hydroxide and calcium dihydrogenphosphate monohydrate powders are used as starting materials so as to prepare a mixed powder of which molar ratio of Ca to P is appropriately controlled and the mixed powder is further mixed and milled in dry-process, so that soft-mechanochemical reaction is rapidly advanced thereby to form xcex2-tricalcium phosphate precursor. Then, when the precursor is subjected to a heat treatment at temperature of 600xc2x0 C. or more, there can be manufactured finely crystallized powder of xcex2-tricalcium phosphate (TCP).
The above soft-mechanochemical reaction is caused even if the dispersing medium such as water or the like is not existing and the reaction is caused by an interaction between acid-base points existing on the surfaces of different material particles. At this time, a mechanochemical dehydrating reaction and an amorphousizing reaction are advanced thereby to produce xcex2-tricalcium phosphate precursor as an intermediate product.
The above mechanochemical dehydrating reaction is quite different from an ordinary heat-dehydrating reaction to be caused by heat energy and the mechanochemical dehydrating reaction is a reaction in which a bonding state of hydroxyl group is changed by the mechanical energy caused in the mixing/milling process. The change of the bonding state of the hydroxyl group takes an important role in forming xcex2-tricalcium phosphate (TCP) precursor by the above soft-mechanochemical compositing reaction. A completion state (degree of advancement) of the above various reactions, composition (purity) and molecular structure of the product or the like are totally evaluated by various analyzing and testing methods such as thermogravimetry-differential thermal analysis (TG-DTA), X-ray diffraction method (XRD) and Fouier transform infrared microscope (FT-IR) or the like.
In the mixing/milling process in the method of this invention, a chemical interaction is mainly taken place in addition to a mere physical mixing of different material particles. The material particle size is changed by the milling operation thereby to increase surface energy per unit volume of the material particles and to increase lattice inconsistencies such as dislocation of crystals and amorphousizing to be caused in a solid body of the material particles. Such increases of the surface energy and the lattice inconsistency also become one factor for promoting the aforementioned soft-mechanochemical compositing reaction.
In a case where the material mixture is treated under the conditions of mixing/milling by dry-process in the method of this invention without adding a dispersion medium to the material mixture, a milled substance (precursor) to be obtained is dried powder, so that there is no need to adopt a drying process which had been deemed to be an essential process for the synthesizing method based on the conventional wet-type mechanochemical reaction method. Therefore, when the precursor formed by the reaction is directly subjected to the heat treatment, fine particle powder of xcex2-tricalcium phosphate crystal can be obtained while an input amount of the heat energy is reduced. The production of xcex2-tricalcium phosphate is due to the blended molar ratio of Ca to P, and hydroxy calcium phosphate can be also produced by changing the molar ratio through a similar process.
As mentioned above, the mixing/milling process in the method of this invention may be performed in accordance with the dry-type mixing method in which the dispersing medium such as water is not added to the material mixture. However, the same effect can be also obtained in accordance with a wet-type mixing method in which the dispersing medium is added to the material mixture to prepare a material slurry having a high solid content of 15-50 wt %, preferably 20-45 wt %, then the material slurry is mixed/milled. In a case where this wet-type mixing method is adopted, the solid content of the material slurry can be greatly increased in comparison with that of the conventional method, it becomes possible to efficiently manufacture calcium phosphate compounds in a short time. In particular, when the aforementioned multi-ring medium type ultrafine mill is used as the milling device for performing the mixing/milling operation, the effective milling operation can be performed with respect to the slurry having a high solid contents and high viscosity.